The broad objectives of this research program are unchanged. We plan, as before, to study the basic physiology of bile formation, including the biophysics of solute and H2O transport between blood and bile, the intra-hepatic distribution and metabolism of materials destined for biliary excretion, and the operation of neural and hormonal control mechanisms. Specific goals for the period covered by the present proposal are to identify the mechanism of bile salt-independent choleresis induced by SC-2644, to describe the kinetics of bile salt exchange in isolated liver cells, to evaluate the role of micellar sequestration in promoting canalicular excretion of organic anions, and to define by autoradiography the steady-state intralobular distribution of bile salts arriving in the afferent blood supply. We will also continue to explore the feasibility of using micropuncture techniques as a means to sampling bile directly from the small ductules in the portal space.